The National Comorbidity Survey - Adolescent (NCS-A) is a survey of 10,000 adolescents being carried out in parallel with the National Comorbidity Survey Replication (NCS-R) and National Comorbidity Survey 2 (NCS-2). The goal of NCS-A is to produce nationally representative data on the prevalences and correlates of mental disorders among youth. SDGE has played a leading role in the development of the diagnostic interview, compilation of a comprehensive battery of risk factors, and conducting the clinical reappraisal of the lay interviewer-based diagnostic assessments using the K-SADS, a clinical diagnostic interview. At NIMH we designed a sub-study to evaluate neuroendocrine hormones in this population-based sample, as described below: There is emerging evidence regarding the importance of the association between neuroendocrine hormones and psychiatric disorders, particularly depression and anxiety; some recent research even suggests that certain hormones such as testosterone and the Dehydroepiandrosterone (DHEA)/cortisol ratio may predict the incidence of depression. However, most of the information on associations between neuroendocrine parameters and psychopathology is based on non-systematic small samples; moreover, there is a general lack of population baseline data on neuroendocrine or reproductive hormones in a nationally representative sample of the age group spanning childhood and adulthood. The lack of population baseline data has also precluded proper evaluation of the intriguing sex and developmental differences in the associations between testosterone and depression, cortisol with both anxiety and depression and the DHEA/cortisol ratio with stress reactivity. The NCS-A, a combined probability and school-based multi-ethnic sample of 10,000 U.S. adolescents, provides an excellent opportunity for the collection of this essential baseline information, as well as information on associations between neuroendocrine parameters and the common mental disorders, particularly mood and anxiety disorders. The primary aims of the NCS-A neuroendocrine hormone study are: o To examine the associations between endocrine measures with anxiety and depression in youth; o To evaluate whether there are differences between hormone levels in youth according to pubertal status; o To assess whether high risk youth without disorders themselves have lower levels of endocrine hormones than those with a history of mood or anxiety disorders; o To examine the influence of gender in moderating the risk and protection conferred by variation in expression of these neuroendocrine measures. In collaboration with Ron Kessler at Harvard University, staff members of the Institute of Survey Research, members of the NMH intramural program, and other external collaborators, Drs. Merikangas and Avenevoli have played an integral role in the National Comorbidity Survey-Adolescent Study (NCS-A). The NCS-A is a nationally representative face-to-face survey of 10,129 adolescents, selected from households and schools, conducted between February 2001 and February 2004. In their homes, participants completed a diagnostic interview (the Composite International Diagnostic Interview (CIDI)) that assessed psychopathology, demographic information, and information on risk and protective factors, and also provided saliva samples before and after the interview. One parent of each participant completed a questionnaire about the participant and his or her family members. Our collaborators at the University of Michigan are currently cleaning the survey data. In the past year, SDGE members have participated in the assessment of validity of the diagnostic interview, consultation of analyses of survey data, and the collection and assay of endocrine samples. Many members of SDGE are assessing the validity of the CIDI-A by coding and comparing interviews using the CIDI and the Schedule for Affective Disorders and Schizophrenia-Child Version. Drs. Merikangas and Avenevoli continue to participate in monthly phone calls and annual meetings regarding plans for the cleaning and analyses of adult and adolescent data. With regard to the biomarkers data, Shelli Avenevoli has coordinated the collection of saliva samples from the NIMH intramural (in conjunction with Kathleen West). During the past year, more than 3000 cortisol assays have been conducted in the MAP laboratory and we are in the process of analyzing these data according to the original study hypotheses. During the next budget year, we should complete the biochemical assays and analyses of these data in collaboration with the Laboratory of Clinical Neuroendocrinology in the Mood and Anxiety Disorders Program. As part of the clinical reappraisal phase of the National Comorbidity Survey (NCS), our section and clinical interviewing staff are reviewing audiotapes of the child interviews (KSADS; respondent and parent reports) to clarify assigned diagnoses. Fifteen interviewers (i.e., psychiatrists, developmental psychologists, clinical social workers, research psychologists) have reviewed tapes, coded interviews, and written short reports identifying areas where discrepancies in diagnoses may have occurred. Dr. Merikangas and staff meet weekly, via conference call, with the staff at Harvard University to discuss progress and resolve diagnostic dilemmas. We are now beginning to conduct the data analyses of the clinical appraisal data to evaluate the level of agreement between lay and clinical interviews, and between maternal and child informants. Our interview team is starting to re-interview all youth who enter the bipolar disorder screening section of the CIDI and a subset of those who enter the conduct disorder sections, as well as a random sample of controls. We expect to re-interview approximately 100 youth from this national probability sample. During the next year, we will focus on conducting the primary data analyses of this unique survey and will present the findings at professional meetings and as publications.